General

Pronunciation:
byoo-des-oh-nide/for-moe-te-rol/glye-koe-pye-roe-late

Trade Name(s)

• Breztri Aerosphere

Ther. Class.

anti-inflammatories (steroidal)

bronchodilators

Pharm. Class.

corticosteroids

long-acting beta2-adrenergic agonists (LABAs)

anticholinergics

Indications

Maintenance treatment of COPD.

Action

Budesonide:  Potent, locally acting anti-inflammatory formoterol:  a beta₂ -adrenergic agonist that stimulates adenyl cyclase, resulting in accumulation of cyclic adenosine monophosphate at beta₂ –adrenergic receptors resulting in bronchodilation glycopyrrolate:  acts as an anticholinergic by inhibiting M3 muscarinic receptors in bronchial smooth muscle resulting in bronchodilation.

Therapeutic Effect(s):

Bronchodilation with decreased airflow obstruction.

Pharmacokinetics

Budesonide

Absorption: Unknown.

Distribution: Extensively distributed to extravascular tissues.

Metabolism and Excretion: Primarily metabolized by the liver by the CYP3A4 isoenzyme into inactive metabolites; primarily excreted in urine and feces as metabolites.

Half-life: 5 hr.

Formoterol

Absorption: Unknown.

Distribution: Extensively distributed to extravascular tissues.

Metabolism and Excretion: Primarily metabolized by the liver by glucuronidation and O-demethylation to inactive metabolites; 62% of drug excreted in urine, 24% excreted in feces.

Half-life: 10 hr.

Glycopyrrolate

Absorption: Unknown.

Distribution: Extensively distributed to extravascular tissues.

Metabolism and Excretion: Primarily metabolized by the liver, with the CYP2D6 isoenzyme playing a minor role in elimination; 85% excreted in urine.

Half-life: 15 hr.

TIME/ACTION PROFILE (improvement in FEV1)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Asthma;
• Acutely deteriorating COPD or acute respiratory symptoms.

Use Cautiously in:

• Systemic corticosteroid therapy (should not be abruptly discontinued when inhaled therapy is started; additional corticosteroids needed during stress or trauma);
• Prolonged immobilization, family history of osteoporosis, postmenopausal status, cigarette smoking, advanced age, or poor nutrition (↑ risk of osteoporosis);
• Narrow-angle glaucoma;
• Seizure disorders;
• Thyrotoxicosis;
• Urinary retention, prostatic hyperplasia, bladder-neck obstruction;
• Diabetes;
• Severe hepatic impairment;
• Severe renal impairment (CCr <30 mL/min) or end-stage renal disease requiring dialysis (use only if expected benefit exceeds potential risk);
• OB:   Safety not established in pregnancy;
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
• Pedi:  Safety and effectiveness not established in children.

Exercise Extreme Caution in:

Concurrent use of MAO inhibitors, tricyclic antidepressants, or drugs that prolong the QTc interval.

Adverse Reactions/Side Effects

CV: arrhythmias, hypertension, tachycardia

EENT: cataracts, glaucoma, sinusitis

Endo: adrenal suppression (high dose, long-term therapy only), hyperglycemia

F and E: hypokalemia

GI: diarrhea, oropharyngeal candidiasis

MS: ↓ bone density, muscle spasms

Resp: bronchospasm, cough, pneumonia

Misc: HYPERSENSITIVITY REACTIONS (including angioedema, urticaria, or rash)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Strong  CYP3A4 inhibitors, including  atazanavir,  clarithromycin,  itraconazole,  ketoconazole,  nefazodone,  nelfinavir, and  ritonavir  may ↑ levels and risk of toxicity.
•  Anticonvulsants,  oral corticosteroids, and  proton pump inhibitors  may ↑ risk of osteoporosis.
• Concurrent use with other  adrenergics  may ↑ adrenergic adverse reactions of formoterol (↑ heart rate, ↑ BP, jitteriness).
•  Xanthine derivatives,  corticosteroids,  diuretics  may ↑ risk of hypokalemia or ECG changes with formoterol.
• ↑ risk of serious adverse cardiovascular effects with  MAO inhibitors,  tricyclic antidepressants,  QT-interval prolonging drugs ; use with extreme caution.
• Effectiveness of formoterol may be ↓ by  beta-blockers ; use cautiously and only when necessary.
• ↑ risk of anticholinergic adverse reactions with glycopyrrolate when used concurrently with other  anticholinergics ; avoid concurrent use.

Route/Dosage

Inhaln (Adults): 2 inhalations twice daily.

Availability

Inhalation aerosol: budesonide 160 mcg/glycopyrrolate 9 mcg/formoterol 4.8 mcg per inhalation in 10.7-g canister (120 inhalations)

Assessment

• Assess lung sounds, pulse, and BP before administration and during peak of medication. Note amount, color, and character of sputum produced.
• Observe for paradoxical bronchospasm (wheezing, dyspnea, tightness in chest) and hypersensitivity reaction (rash; urticaria; swelling of the face, lips, or eyelids). If condition occurs, withhold medication and notify health care professional immediately.
• Monitor patient for signs of hypersensitivity reactions (difficulties in breathing or swallowing; swelling of tongue, lips, and face; urticaria; skin rash) during therapy. Discontinue therapy and consider alternative if reaction occurs.

Lab Test Considerations:

May ↑ serum glucose and ↓ serum potassium.

Implementation

• Inhaln Administer as 2 inhalations twice daily, morning and evening. Shake well prior to use. Prime by releasing 4 sprays into air away from face before 1st use and by releasing 2 sprays if unused for more than 7 days. After inhalation, rinse mouth with water without swallowing. See medication administration techniques for use of metered-dose inhalers.

Patient/Family Teaching

• Instruct patient to use medication as directed. Do not discontinue therapy without discussing with health care professional, even if feeling better. If a dose is missed, skip dose and take next dose at regularly scheduled time. Do not double doses. Use a rapid-acting bronchodilator if symptoms occur before next dose is due. Caution patient not to use more than 2 times a day; may cause adverse effects, paradoxical bronchospasm, or loss of effectiveness of medication. Instruct patient to review  Medication Guide  before starting therapy and with each Rx refill in case of changes.
• Advise patient that inhaler should be discarded when display window indicates zero or 3 mo (120-inhalation canister) or 3 wk (28-inhalation canister) after removal of canister from pouch, whichever comes first. Never immerse the canister into water to determine the amount remaining in the canister ("float test").
• Caution patient not to use medication to treat acute symptoms. A rapid-acting inhaled beta-adrenergic bronchodilator should be used for relief of acute asthma attacks. Notify health care professional immediately if symptoms get worse or more inhalations than usual are needed from rescue inhaler.
• Advise patient to rinse the mouth with water without swallowing after inhalation to help reduce the risk of getting a fungus infection (thrush) in the mouth and throat.
• Instruct patient to contact health care professional immediately if shortness of breath is not relieved by medication or nausea, vomiting, shakiness, headache, fast or irregular heartbeat, sleeplessness, or signs and symptoms of narrow angle glaucoma (eye pain or discomfort, blurred vision, visual halos or colored images, red eyes), urinary retention (difficulty passing urine, painful urination) or pneumonia (increase in mucus (sputum) production, change in mucus color, fever, chills, increased cough, increased breathing problems) occur.
• Advise patient to consult health care professional before taking any Rx, OTC, or herbal products or alcohol concurrently with this therapy. Caution patient also to avoid smoking and other respiratory irritants.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Bronchodilation with decreased airflow obstruction.